Zyfrel

Name: Zyfrel

Patient information

ZYFREL
(hydrocodone bitartrate and acetaminophen) Oral Solution, 7.5 mg/325 mg per 15 mL

Summary

ZYFREL (pronounced [Zye-FREL]) is used to relieve moderate to moderately severe pain. You should not take ZYFREL if you are allergic to hydrocodone or acetaminophen. The most common side effects of ZYFREL are abdominal pain, dizziness, drowsiness, light-headedness, nausea, shortness of breath, unusual tiredness, and vomiting. Take this medicine as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Uses

ZYFREL is an analgesic used to relieve moderate to moderately severe pain. ZYFREL is a combination product containing hydrocodone (hye-droe-KO-done) bitartrate and acetaminophen (a-seat-a-MIN-ohfen). Hydrocodone is a narcotic pain reliever and a cough suppressant. Acetaminophen is a non-narcotic pain reliever and fever reducer. A narcotic analgesic and acetaminophen used together may provide better pain relief than either product used alone. If you have any questions, please call your doctor or pharmacist.

General Cautions

  • Do not take this drug if you have allergies or unusual reactions to narcotic pain relievers or acetaminophen because it is likely that you may also be allergic to ZYFREL.
  • This product may inhibit your mental and physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while you are taking this product.
  • This medicine may not be right for you. Check with your doctor or pharmacist, if you:
    • are pregnant.
    • are nursing.
    • are taking other medications: narcotic pain relievers; allergy medicines; antidepressant medicines; acetaminophen-containing medicines or other medicines that cause central nervous system depression, including alcohol.
    • have other medical problems: a history of drug or alcohol abuse; recent head injury; emphysema, asthma, or other chronic lung disease; liver disease, kidney disease; underactive thyroid, Addison's disease, enlarged prostate or difficulty urinating.

Proper Use

Take this medicine as directed by your doctor. Do not share it with anyone else. This medicine can cause drug dependence and has the potential for abuse. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If you think that this medicine is not working properly after taking it for some time, do not increase the dose. Check with your doctor or pharmacist.

Dosing

The dose of this medication will be different for different patients. Follow the directions provided by your doctor. The following information includes only the average doses of this medication. If your dose is different, do not change doses unless your doctor tells you to do so.

BODY WEIGHT APPROXIMATE AGE DOSE every 4 to 6 hours MAXIMUM TOTAL DAILY DOSE (6 doses per day)
12 to 15 kg 27 to 34 lbs. 2 to 3 years % teaspoonful = 3.75 mL 4½ teaspoonfuls = 22.5 mL
16 to 22 kg 35 to 50 lbs. 4 to 6 years 1 teaspoonful = 5 mL 6 teaspoonfuls = 30 mL
23 to 31 kg 51 to 69 lbs. 7 to 9 years 1½ teaspoonfuls = 7.5 mL 9 teaspoonfuls = 45 mL
32 to 45 kg 70 to 100 lbs. 10 to 13 years 2 teaspoonfuls = 10 mL 12 teaspoonfuls = 60 mL
46 kg and up 101 lbs. and up 14 years to adult 1 Tablespoonful = 15 mL 6 Tablespoonfuls = 90 mL

It is very important that ZYFREL be dosed accurately. A household teaspoon or tablespoon is not an accurate measuring device, especially when one-half or three-fourths of a teaspoonful is to be measured.

Since a household teaspoon is not accurate and can be mixed-up with a tablespoon (which can cause over dosage), it is strongly recommended that you obtain and use a proper measuring device. Ask your doctor or pharmacist for help to find an oral device that can measure the needed dose properly and ask for help if you do not understand how to use the oral device.

Missed Dose

  • To avoid a possible overdose, it is important that you do not take more than a single dosage at one time, or that you don't take doses at intervals less than 4 hours apart.
  • If you miss taking a dose of ZYFREL, take it as soon as you remember. However, make sure to wait at least 4 hours before taking your next dose.
  • If you missed taking a dose, and it is almost time for your next dose, skip the missed dose and take your medicine as scheduled.
  • Do not double the prescribed dose.

Possible Side Effects

Side effects you may experience include abdominal pain, constipation, difficulty urinating, dizziness, drowsiness, fear, fuzzy thinking, general feeling of discomfort or illness, light-headedness, mood changes, nausea, nervousness, rash, shortness of breath, slower reactions, unusual tiredness, and vomiting.

Call your doctor if these effects continue or are bothersome.

Side effects not listed above may sometimes occur. If you notice any other effects, check with your doctor.

Storage

  • Keep out of reach of children.
  • Store at room temperature (protect from heat, do not refrigerate).
  • Keep in original labeled bottle.
  • Discard medicines that are old or no longer needed.
  • Even a single overdose of this medicine may be a life-threatening situation. If you suspect that you or someone else may have taken more than the prescribed dose of this medicine, contact your local poison control center or emergency room immediately. This medicine was prescribed for your particular condition. Do not use it for another condition or give the drug to others.
  • This leaflet provides a summary of information about ZYFREL. If you have any questions or concerns, or want more information about ZYFREL, contact your doctor or pharmacist. Your pharmacist also has a longer leaflet about ZYFREL that is written for health professionals that you can ask to read.

What do I need to tell my doctor BEFORE I take Zyfrel?

  • If you have an allergy to hydrocodone, acetaminophen, or any other part of Zyfrel.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Lung or breathing problems like asthma, trouble breathing, or sleep apnea; high levels of carbon dioxide in the blood; or stomach or bowel block or narrowing.
  • If you are taking any of these drugs: Buprenorphine, butorphanol, nalbuphine, or pentazocine.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any of these drugs: Linezolid or methylene blue.

This is not a list of all drugs or health problems that interact with Zyfrel.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

How is this medicine (Zyfrel) best taken?

Use Zyfrel as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food. Take with food if it causes an upset stomach.
  • Measure liquid doses carefully. Use the measuring device that comes with this medicine. If there is none, ask the pharmacist for a device to measure Zyfrel (hydrocodone and acetaminophen liquid).
  • Be sure that you know how to measure your dose. Dosing errors can lead to accidental overdose and death. If you have any questions, talk with your doctor or pharmacist.

What do I do if I miss a dose?

  • If you take this medicine on a regular basis, take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Many times Zyfrel is taken on an as needed basis. Do not take more often than told by the doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Very bad dizziness or passing out.
  • Feeling very sleepy.
  • Trouble breathing, slow breathing, or shallow breathing.
  • Feeling confused.
  • Trouble walking.
  • Very hard stools (constipation).
  • Very bad belly pain.
  • Feeling very tired or weak.
  • Not able to pass urine or change in how much urine is passed.
  • Hearing loss.
  • Change in hearing.
  • Chest pain or pressure or a fast heartbeat.
  • Fever or chills.
  • Sore throat.
  • Mood changes.
  • Very bad headache.
  • Trouble passing urine.
  • Any unexplained bruising or bleeding.
  • Change in eyesight.
  • Seizures.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen if you take this medicine with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Zyfrel?

  • Store at room temperature. Do not refrigerate or freeze.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Zyfrel Description

Hydrocodone bitartrate and acetaminophen is available in liquid form for oral administration.

Hydrocodone bitartrate is an opioid analgesic and antitussive and occurs as fine, white crystals or as a crystalline powder. It is affected by light. The chemical name is 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula:

C18H21NO3∙C4H6O6∙2½ H2O MW = 494.490

Acetaminophen, 4'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

C8H9NO2 MW = 151.16

Zyfrel Oral Solution contains:

Per 5 mL Per 15 mL
Hydrocodone Bitartrate 2.5 mg 7.5 mg
Acetaminophen 108 mg 325 mg

In addition, the liquid contains the following inactive ingredients: citric acid anhydrous, glycerin, methylparaben, polyethylene glycol 400, propylene glycol, propylparaben, purified water, saccharin sodium, sodium citrate dihydrate, sorbitol solution, sucralose, sucrose, and bubble gum flavor.

Medication guide

Medication Guide
Zyfrel™ (zye-FREL)
Oral Solution, CII
This Medication Guide has been approved by the U.S. Food and Drug Administration. HI236 Issued: 01/2017
Zyfrel Oral Solution is:
  • A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain severe enough to require an opioid pain medicine and for which alternative treatments are inadequate and when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.
  • An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.
Important information about Zyfrel Oral Solution:
  • Get emergency help right away if you take too much Zyfrel Oral Solution (overdose). When you first start taking Zyfrel Oral Solution, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur.
  • Taking Zyfrel Oral Solution with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.
  • Never give anyone else your Zyfrel Oral Solution. They could die from taking it. Store Zyfrel Oral Solution away from children and in a safe place to prevent stealing or abuse. Selling or giving away Zyfrel Oral Solution is against the law.
Do not take Zyfrel Oral Solution if you have:
  • severe asthma, trouble breathing, or other lung problems.
  • a bowel blockage or have narrowing of the stomach or intestines.
  • known hypersensitivity to hydrocodone or acetaminophen, or any ingredient in hydrocodone and acetaminophen oral solution.
Before taking Zyfrel Oral Solution, tell your healthcare provider if you have a history of:
  • head injury, seizures
  • problems urinating
  • liver, kidney, thyroid problems
  • pancreas or gallbladder problems
  • abuse of street or prescription drugs, alcohol addiction, or mental health problems.
Tell your healthcare provider if you are:
  • pregnant or planning to become pregnant. Prolonged use of Zyfrel Oral Solution during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated.
  • breastfeeding. Zyfrel Oral Solution passes into breast milk and may harm your baby.
  • taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking Zyfrel Oral Solution with certain other medicines can cause serious side effects that could lead to death.
  • taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking Zyfrel Oral Solution with certain other medicines can cause serious side effects that could lead to death.
When taking Zyfrel Oral Solution:
  • Do not change your dose. Take Zyfrel Oral Solution exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
  • Always use a calibrated measuring device for Zyfrel Oral Solution to correctly measure your dose. A household teaspoon or tablespoon is not an adequate measuring device. Given the inexactitude of the household spoon measure and the possibility of using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that caregivers obtain and use a calibrated measuring device.
BODY WEIGHT APPROXIMATE AGE DOSE
every 4 to 6 hours		 MAXIMUM TOTAL DAILY DOSE
(6 doses per day)
12 to 15 kg
27 to 34 lbs.		 2 to 3 years ¾ teaspoonful = 3.75 mL 4½ teaspoonfuls = 22.5 mL
16 to 22 kg
35 to 50 lbs.		 4 to 6 years 1 teaspoonful = 5 mL 6 teaspoonfuls = 30 mL
23 to 31 kg
51 to 69 lbs.		 7 to 9 years 1½ teaspoonfuls = 7.5 mL 9 teaspoonfuls = 45 mL
32 to 45 kg
70 to 100 lbs.		 10 to 13 years 2 teaspoonfuls = 10 mL 12 teaspoonfuls = 60 mL
46 kg and up
101 lbs. and up		 14 years to adult 1 Tablespoonful = 15 mL 6 Tablespoonfuls = 90 mL
  • Take your prescribed dose. The usual adult dosage is one tablespoonful (15 mL) every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablespoonfuls. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.
  • Call your healthcare provider if the dose you are taking does not control your pain.
  • If you have been taking Zyfrel Oral Solution regularly, do not stop taking Zyfrel Oral Solution without talking to your healthcare provider.
  • After you stop taking Zyfrel Oral Solution, the unused solution should be disposed of by flushing down the toilet.
While taking Zyfrel Oral Solution DO NOT:
  • Drive or operate heavy machinery, until you know how Zyfrel Oral Solution affects you. Zyfrel Oral Solution can make you sleepy, dizzy, or lightheaded.
  • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with Zyfrel Oral Solution may cause you to overdose and die.
The possible side effects of Zyfrel Oral Solution:
  • constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.
Get emergency medical help if you have:
  • trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.

These are not all the possible side effects of Zyfrel Oral Solution. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov

Manufactured for: Hawthorn Pharmaceuticals, Inc., Morristown, NJ 07960, call1-800-793-2145

PRINCIPAL DISPLAY PANEL - 473 mL Bottle Label

NDC 63717-893-16

Zyfrel™ CII
(hydrocodone bitartrate and
acetaminophen) Oral Solution
7.5 mg/325 mg per 15 mL

Contains: Per
5 mL		 Per
15 mL
Hydrocodone
  Bitartrate		 2.5 mg 7.5 mg
Acetaminophen 108 mg 325 mg

PHARMACIST: Dispense the
Medication Guide with the
drug product.

Rx Only

HAWTHORN
PHARMACEUTICALS, INC.

16 fl oz (473 mL)

Zyfrel 
hydrocodone bitartrate and acetaminophen solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:63717-893
Route of Administration ORAL DEA Schedule CII    
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Hydrocodone Bitartrate (Hydrocodone) Hydrocodone Bitartrate 7.5 mg  in 15 mL
Acetaminophen (Acetaminophen) Acetaminophen 325 mg  in 15 mL
Inactive Ingredients
Ingredient Name Strength
Anhydrous Citric Acid  
Glycerin  
Methylparaben  
Polyethylene Glycol 400  
Propylene Glycol  
Propylparaben  
Saccharin Sodium  
Sodium Citrate, Unspecified Form  
Sorbitol  
Sucralose  
Sucrose  
Water  
Product Characteristics
Color      Score     
Shape Size
Flavor BUBBLE GUM Imprint Code
Contains     
Packaging
# Item Code Package Description
1 NDC:63717-893-16 473 mL in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090468 04/14/2016
Labeler - Hawthorn Pharmaceuticals, Inc. (118049704)
Establishment
Name Address ID/FEI Operations
Woodfield Pharmaceuticals 079398730 MANUFACTURE(63717-893)
Revised: 01/2017   Hawthorn Pharmaceuticals, Inc.
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